Osmotic diuretics

Definitions & Key takeaways

Diuretics are a class of drugs used to reduce the amount of water in the body, by raising the production of urine. Once filtered in the glomerulus, osmotic diuretics do not get reabsorbed. This increases the osmotic pressure in the kidneys and causes water to leave blood into the forming urine. The main effect of osmotic diuretics is applied in parts of the nephron that are permeable to water, mainly the proximal tubule, descending part of the loop, and the collecting tubules. Examples of osmotic diuretics include mannitol, glycerin, and isosorbide.

Chapters:

Watch video only

Introduction0:00–0:28

Diuretics are medications that act on the kidneys to increase production of urine, and therefore, elimination of water from the body.
There are 5 main types of diuretics: carbonic anhydrase inhibitors; loop diuretics; thiazide and thiazide-like diuretics; potassium sparing diuretics; and last but not least, osmotic diuretics - which we’ll get intimately acquainted with during this video.

Physiology0:28–1:19

Now, the basic unit of the kidney is called a nephron, and each nephron is made up of a glomerulus, which filters the blood.
The filtered content goes through the renal tubule, where excess waste, and molecules (such as ions and water), are removed or filtered through an exchange between the tubule and the peritubular capillaries.
So the renal tubule plays a huge role in secretion and reabsorption of fluid and ions - such as sodium, potassium, and chloride - in order to maintain homeostasis - or the the balance of fluid and ions in our body.
The renal tubule has a few segments of its own: the proximal convoluted tubule; the U-shaped loop of Henle, with a thin descending, a thin ascending, and a thick ascending limb; and finally, the distal convoluted tubule, which empties into the collecting duct, which collects the urine.

Mechanism of Action1:19–2:58

The prototypal osmotic diuretic is mannitol; other osmotic diuretics like glycerin and isosorbide are rarely used. Following IV administration, mannitol travels through the bloodstream and acts like you’d expect an osmotically active molecule to act: it sucks water out of the cells it encounters along the way, and all that extra water reaches the kidneys as increased renal blood flow.
Once at the kidneys, it gets secreted by the glomerulus into the renal tubule. Some of the segments of the renal tubule, like the proximal convoluted tubule and the thin descending limb, are freely permeable to water.
So any osmotic agent that ends up here will tend to make water stay inside the tubule, rather than be reabsorbed. Now, this increased volume leads to increased flow rate through the nephron, so there’s less time for the sodium to be reabsorbed.
This causes a small increase in sodium loss, but much more water is lost, so mannitol is considered an aquaretic diuretic, meaning it promotes water excretion without increasing the loss of electrolytes.
This can come in handy when we need to remove water from the body, but only in certain conditions. Unlike other diuretics which are often used to treat hypertension and edematous states, osmotic diuretics are mainly used to lower intraocular pressure in glaucoma and before ophthalmologic procedures; or to lower intracranial pressure, such as following head trauma.
Since mannitol also increases renal blood flow, it can be used to flush away harmful substances that builds up in the kidney.
Examples include myoglobin from rhabdomyolysis, which is the break down of muscles, and hemoglobin from hemolysis, which is the breakdown of red blood cells.

Side Effects2:58–3:44

Now for side effects, first off, right after mannitol enters the bloodstream and before it gets excreted, it pulls intracellular fluid into the extracellular space, so it could worsen edematous states like pulmonary edema.
When more water gets pulled into the blood vessels, the concentration of sodium will go down, causing hyponatremia. This is especially likely to happen in individuals with renal impairment, where the kidneys can’t excrete the mannitol, and in congestive heart failure, where the heart can’t handle the increased plasma volume.
Now, when mannitol makes it to the kidney, we start losing water rapidly, so there’s a risk of dehydration if water replacement is not adequate.
Since more water is lost than other electrolytes, there’s a high risk of developing hypernatremia and hyperkalemia. Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts!

Memory Palace3:44–4:42

We can use the Osmosis robot in a bathroom to help you remember the osmotic diuretics. He’s got some mistletoe dangling from his head for mannitol, which is the most commonly used medication in this class.
For indications, let’s have a running sink that contains a brain with a pair of bulging eyes for increased intracranial pressure and glaucoma.
In the toilet, we are flushing down a red blood cell and a muscular arm for hemolysis and rhabdomyolysis. For side effects, we can have a bathtub full of water to represent its initial effects in the blood stream.
There’s an empty salt shaker floating in the tub for hyponatremia, and waterlogged lungs sunk to the bottom, for pulmonary edema.
For the later stages where we lose too much water, we can have a thirsty, shriveled up man representing dehydration. He’s carrying a full salt shaker and a large banana for hypernatremia and hyperkalemia.

Review4:42–5:22

All right, as a quick recap… mannitol is the prototypal osmotic diuretic, and it acts by decreasing water reabsorption in the proximal convoluted tubule and thin descending limb.
It’s given intravenously, mainly for lowering intraocular pressure before ophthalmologic procedures, and lowering intracranial pressure.
The main risks associated with mannitol use are: extracellular volume expansion and hyponatremia, and, at the other end of the spectrum, dehydration, hypernatremia, and hyperkalemia.
Contraindications include severe kidney damage, dehydration, heart failure, and pulmonary edema. But wait, there’s more: Here’s a mind map with all of the mnemonics.

Mind Map5:22–5:32

Go ahead and pause the video so you can test yourself to see what you remember. Stay tuned for the answers after the credits.